Identification of any publication, patent, or patent application in this section or any section of this application is not an admission that such publication is prior art to the present invention.
The preparation of diazaspirodecan-2-ones for example, 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one, for example, (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4.5]decan-2-one (the compound of Formula I) has been described in U.S. Pat. No. 7,049,320 (the '320 patent), issued May 23, 2006, the disclosure of which is incorporated herein in its entirety by reference.

The compounds described in the '320 patent are classified as tachykinin compounds, and are antagonists of neuropeptide neurokinin-1 receptors (herein, “NK-1” receptor antagonists). Other NK1 receptor antagonists and their synthesis have been described, for example, those described in Wu et al, Tetrahedron 56, 3043-3051 (2000); Rombouts et al, Tetrahedron Letters 42, 7397-7399 (2001); and Rogiers et al, Tetrahedron 57, 8971-8981 (2001) and in published International Application No. WO05/100358, each of which is incorporated herein in their entirety by reference. A process for preparing the compound of Formula I is also disclosed in U.S. Application No. 2008/003640, filed Mar. 20, 2008 (the '640 application).
“NK-1” receptor antagonists have been shown to be useful therapeutic agents, for example, in the treatment of pain, inflammation, migraine, emesis (vomiting), and nociception. Among many compounds disclosed in the above-mentioned '320 patent are several novel diazaspirodecan-2-ones, including the compound of Formula I, which are useful in the treatment of nausea and emesis associated with any source of emesis, for example, emesis associated with recovery from anesthesia or chemotherapy treatments (Chemotherapy-induced nausea and emesis, herein, CINE).
The synthesis method for preparing the compound of Formula I described in the '320 patent generally follows Scheme A in the provision of 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one compounds.

The process for the preparation of the compound of Formula I described in the '320 patent is carried out in 18 individual steps from commercially available starting materials, and in many steps of the process described in the '320 patent, intermediate compounds must be isolated or isolated and purified before use in a subsequent step, often utilizing column chromatography for that purpose. In general, the synthetic scheme described in the '320 patent consumes a larger than desirable percentage of starting and intermediate compounds in the production of unwanted isomers.
The process for the preparation of the compound of Formula I described in the '640 application generally follows Scheme B:

The process described in Scheme B comprises about half the number of steps compared to Scheme A and produces the compound in greater yield than Scheme A, however, both schemes suffer from poor diastereoselectivity.
Accordingly, what is needed is a more convergent and efficient process which has improved diastereoselectivity.